Mycobacterium tuberculosis is a highly successful pathogen that can infect, persist, and cause progressive disease in humans and experimental animals with apparently normal immune responses. This implies that Mycobacterium tuberculosis has evolved mechanisms to avoid elimination by normal mechanisms of immunity. Individuals that are infected with Mycobacterium tuberculosis develop apparently appropriate cellular immune responses with priming, expansion, differentiation, and trafficking of antigen specific CD4+ and CD8+ T-cells resulting in interferon gamma (IFNγ) and tumor necrosis factor (TNFα) production at the site of infection. The inability to clear Mycobacterium tuberculosis despite this immune response suggests that Mycobacterium tuberculosis may interfere with distal effector events. Defective recognition of infected macrophages by T cells and/or defective responses of infected macrophages to effectors of adaptive immunity may contribute to the ability of Mycobacterium tuberculosis to persist and progress. One specific mechanism that could permit Mycobacterium tuberculosis to avoid elimination by the immune response is inhibition of macrophage responses to IFNγ, an important effector of immunity to intracellular pathogens. Indeed, while IFNγ is capable of stimulating macrophages to kill intracellular Toxoplasma, Leishmania, Legionella, and Chlamydia, it has been reported that IFNγ is incapable of stimulating macrophages to kill Mycobacterium tuberculosis in vitro unless IFNγ is used to prime macrophages prior to infection. Moreover, experiments in mice have provided evidence that virulent Mycobacterium tuberculosis evades IFNγ-dependent mechanisms of immune control in vivo.
The currently available vaccine against Mycobacterium tuberculosis is based on a spontaneously-arising attenuated strain of Mycobacterium bovis. However, this vaccine has been insufficient to control the human tuberculosis pandemic, probably as a result of the ability of Mycobacterium tuberculosis to evade human immune response. Therefore, there is a need for new vaccines and treatments that can reduce or abrogate Mycobacterium tuberculosis evasion of hosts' immune responses.